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Can Mosquitoes Fight Malaria?

Scientists can build a mosquito that resists infection, but getting the insects to pass along the gene is a harder task

We may not have flying cars, and our shower curtains inevitably turn moldy after several months, but, to their credit, scientists can engineer a mosquito resistant to Plasmodium, the pathogen that causes malaria in people. Molecular biologists now can manufacture a gene that blocks the infection from fully forming, and inject it into a batch of mosquito eggs. To track the gene's success over generations, the researchers include a marker that, when active, gives each altered offspring a bulging pair of neon green eyes.

The idea behind these tiny green lights was that they might help researchers control the disease that kills more than a million people a year—particularly in impoverished nations. This notion gained strength a few years ago, when a group of researchers found that mosquitoes carrying Plasmodium laid fewer eggs and lived shorter lives than those that buzzed about infection free. It stood to reason, then, that genetically altered insects—called "transgenic" mosquitoes—would, in the long-run, fair better than their wild cousins.

Inside labs around the world, however, this logic did not always hold true. Scientists filled cages half with wild and half with transgenic mosquitoes. Several life cycles later, they censused the insect population and found that, at best, the cages remained half-filled with green eyes. More often, the wild eyes had it.

Recently, a group of researchers at Johns Hopkins University tried again—with a twist. Instead of feeding the mosquitoes regular blood, as the previous experiments had, the Hopkins group fed the insects blood infected with Plasmodium. "Indeed, as generations passed, the proportion of transgenic mosquitoes increased," says Marcelo Jacobs-Lorena, a co-author of the study, which appeared in the Mar. 19 Proceedings of the National Academy of Science. After nine generations, some 70 percent of the population flashed those glowing greens. "Under these conditions," he says, "they were fitter."

Among infectious disease researchers, such a finding would seem packed with promise. "The first reaction is, well, here you go," says Jacobs-Lorena. But the excitement is tempered by several reservations. The first is whether the work could translate to human blood (in the experiment, the mosquitoes fed on infected mice). Jacobs-Lorena believes it would, but even so, releasing genetically altered insects into the wild could also let loose a furious ethical debate.

A more immediate problem exists, however. In wild populations, only 10 to 20 percent of mosquitoes transmit the disease, says parasitologist Hilary Hurd of Keele University, in England, who was not affiliated with the study. Sure, green eyes become the norm in populations that begin with an even roster of altered mosquitoes. But, when outnumbered greatly, could enough malaria-resistant mosquitoes pass on their genes to make a difference? "I am doubtful," says Hurd, a skepticism echoed by Jacobs-Lorena.

It would help matters if some force could drive the desired gene through the population. "That's the biggest remaining burden," says Jacobs-Lorena, "to find this so-called 'drive mechanism.'" Relief for this burden could be getting closer—despite coming from a lab across the country studying not mosquitoes but fruit flies. A group of researchers in California has found a way to make certain genes spray through a population at a rate greater than chance.

Put generally, the highly technical method "uses some trick to cause the death of a chromosome that doesn't carry the element"—in this case, the malaria-resistant gene—says Bruce A. Hay of the California Institute of Technology, who co-authored the study published in the Apr. 27 Science. The researchers call this trickster chromosome Medea, named for Euripides' tragic heroine who killed her own children to spite the husband who abandoned her. When Hay and his colleagues infused some fruit flies with Medea and put them in a cage with unaltered flies, every insect showed signs of the element within 10 or 11 generations. "The average fitness of wild type chromosomes goes down whenever Medea is in the population," he says.

The two studies already have struck a romance: "I think this is quite promising," says Jacobs-Lorena. "If one can transfer this technology to mosquitoes, that could be quite powerful." Researchers would have to create a tight lock between Medea, the driver, and the transgene, the passenger carrying the critical briefcase. "If one could do this in an area relatively quickly, with the driver helping to move [the transgene] rapidly, you have an opportunity to break the cycle of infection," says Hay. "Once Plasmodium has nowhere to replicate, then it's gone."

Those are two big "ifs," and the researchers say they have several generations of studies to go through before removing any doubt. But in time—perhaps in as few as five years, says Hay—the two might even have themselves a swarm of bugs with beautiful green eyes. A healthy swarm.

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